Nutritional compositions containing phosphatidylserine powder

ABSTRACT

Phosphatidylserine powder compositions of the present invention were found to provide more homogeneous dispersion and demonstrate reduced sedimentation, compared to conventional phosphatidylserine powders, when mixed without processing by high pressure homogenization in water or other liquids. The composition of the present invention comprises phosphatidylserine and at least 80% (w/w) of the composition has a particle size of 500 microns or less. Nutritional, nutraceutical, or pharmaceutical compositions including the phosphatidylserine powder compositions of the present invention are also provided. Process for preparing phosphatidylserine powder compositions according to the present invention is also provided and includes sieving.

FIELD OF THE INVENTION

The present invention refers to PS preparations with predeterminedparticle size.

BACKGROUND OF THE INVENTION

Phosphatidylserine (PS), which is the main acid phospholipid inmammalian plasma membrane, has been shown to play a key role in thefunctioning of neuron membranes and to alter multiple neurochemicalsystems (See Vance et al. Metabolism and functions ofphosphatidylserine. Prog. Lipid Res. 2005; 44:207-234). Supplementationof PS to animal models has been shown to attenuate neuronal effects ofaging, as well as restoring normal memory in a range of tasks. In human,administration of PS to subjects with age-associated memory impairment,as well as to mild cognitive impairment patients, resulted with aconsistent improvement of performance in memory tests. Studies conductedon children and adolescents tested the effects of PS supplementation onvarious cognitive and behavior aspects. These studies attest to theability of PS to improve memory, attention and more in children, as wellas to the safety of PS in children (See Hirayama et al. Effect ofphosphatidylserine administration on symptoms ofattention-deficit/hyperactivity disorder in children. AgroFOOD industryhi-tech. 2006; 17:32-36).

Unfortunately, mixing conventional PS powder preparations or PSpreparations in which more than 20% (w/w) of the powder has a particlesize of above 500 microns with nutritional or nutraceutical compositionsoften result in a non-homogeneous dispersion that contains floatingvisible particles and/or sediments and/or interferes with the structureof chewable matrixes.

Additional problem is the reduced stability of conventional PS powder inwater medium and other matrixes.

Previous solutions for the non-homogeneous problem include adding the PSpowder in the early preparation stage of certain nutritionals ornutraceutical powders. In such cases, the preparation is based on a highpressure homogenization in water followed by spray drying to obtain thedry powder. The addition of the PS powder before pressure homogenizationwill ensure that the final powder will have the required properties whenmixed with an aqueous solution. Nevertheless, this order of preparationexposes the PS powder to a long and harmful exposure to oxygen, heat,and water thereby increasing the likelihood of degradation and oxidationof the PS.

Furthermore, in large scale production, adding the PS powder prior tospray drying stage causes logistic problems and creates difficulties tomanufacturers. Adding the PS to the final nutritional or nutraceuticalproduct, in a dry blending stage, may give the manufacturers the abilityto get high flexibility between batches and avoid cross-contaminates.

The present invention provides PS preparations with predeterminedparticle size that may be added to final nutritional, nutraceutical, orpharmaceutical compositions. These novel PS preparations have increasedstability, are homogenous in certain water mediums, and enable thestability of solid and elastic mediums.

SUMMARY OF THE INVENTION

The present invention provides a phosphatidylserine powder compositioncomprising a phosphatidylserine; wherein at least 80% (w/w) of thephosphatidylserine powder composition has a particle size of 500 micronsor less. Preferably the particle size of the phosphatidylserine powdercomposition is 400 microns or less, more preferably 350 microns or less,even more preferably 300 microns or less, even more preferably 250microns or less, even more preferably 200 microns or less, and mostpreferably 150 microns or less. The percentage by weight of thephosphatidylserine powder that satisfies the aforementioned particlesize is preferably at least 85% (w/w), more preferably at least 90%(w/w), even more preferably at least 95% (w/w), and most preferable atleast 97% (w/w). Preferably less than 20% (w/w) of the powder hasparticle size above 500 microns, at times less than 15% (w/w) at timesless than 10% (w/w), at times less than 8% (w/w), at times less than 5%(w/w), at times less than 3% (w/w) and at times less than 1% (w/w).

In certain other non-limiting embodiments of the present invention, thephosphatidylserine powder composition is prepared from a natural source,synthetic source, semisynthetic source, or a combination thereof. Incertain other non-limiting embodiments of the present invention, thephosphatidylserine is prepared using a monophasic reaction, a bi-phasicreaction, or a combination thereof. In certain other non-limitingembodiments of the present invention, the phosphatidylserine is preparedusing a mono-phasic reaction and purified using an organic solvent. Incertain other non-limiting embodiments of the present invention, theorganic solvent is an alcohol solvent. In certain other non-limitingembodiments of the present invention, the phosphatidylserine is preparedusing a bi-phasic reaction. In certain other non-limiting embodiments ofthe present invention, when mixed in water without processing by highpressure homogenization, the powder composition disperses morehomogeneously and demonstrates reduced sedimentation in comparison toconventional PS powder preparations, or with a PS preparation in whichmore than 20% (w/w) of the PS preparation has a particle size of above500 microns. In certain other non-limiting embodiments of the presentinvention, the powder composition is mixed with a powder nutritional,nutraceutical, or pharmaceutical composition to form a mixture, and whenthe mixture is mixed with water without processing by high pressurehomogenization, the mixture disperses more homogeneously anddemonstrates reduced sedimentation compared to a mixture of a powdernutritional, nutraceutical, or pharmaceutical composition andconventional PS powder preparations or a PS preparation in which morethan 20% (w/w) of the PS preparation has a particle size of above 500microns. In certain other non-limiting embodiments of the presentinvention, the powder composition when mixed without processing by highpressure homogenization with a liquid nutritional, nutraceutical, orpharmaceutical composition more homogeneously disperses and demonstratesreduced sedimentation compared to conventional PS powder preparations,or a PS preparation in which more than 20% (w/w) of the PS preparationhas a particle size of above 500.

The present invention also provides a nutritional, pharmaceutical, ornutraceutical composition or a functional or medical food comprising anyone of the phosphatidylserine powder compositions disclosed above.

In certain other non-limiting embodiments of the present invention, thenutritional or nutraceutical composition is a biscuit, pastry, cake,bread, cereal, bar, snack, pill, tablet, pellets, dragees, capsule, softgel, syrup, baby formula, adult formula, medical nutrition product,candy, gummy, or confectionary. In certain other non-limitingembodiments of the present invention, the nutritional, nutraceutical, orpharmaceutical composition maintains a uniform appearance. In certainother non-limiting embodiments of the present invention, thenutritional, nutraceutical, or pharmaceutical composition maintainselastic stability during storage. In certain other non-limitingembodiments of the present invention, the bulk density of thephosphatidylserine powder composition in the nutritional, nutraceutical,or pharmaceutical composition is 0.2 to 0.7 g/ml. In certain othernon-limiting embodiments of the present invention, the dosage unit ofthe phosphatidylserine powder composition in the nutritional,nutraceutical, or pharmaceutical composition is 10 mg to 1000 mg. Incertain other non-limiting embodiments of the present invention, thenutritional, nutraceutical, or pharmaceutical composition is a liquid.In certain other non-limiting embodiments of the present invention, thenutritional, nutraceutical, or pharmaceutical composition is a powder.In certain other non-limiting embodiments of the present invention, thenutritional, nutraceutical, or pharmaceutical composition contains atleast one protein and at least one carbohydrate. In certain othernon-limiting embodiments of the present invention, thephosphatidylserine powder is at least 0.05% (w/w) of the nutritional,nutraceutical, or pharmaceutical composition. In certain othernon-limiting embodiments of the present invention, the nutritional,nutraceutical, or pharmaceutical composition comprises aphosphatidylserine powder composition prepared from a natural source,synthetic source, semisynthetic source, or a combination thereof. Incertain other non-limiting embodiments of the present invention, thenutritional, nutraceutical, or pharmaceutical composition comprises aphosphatidylserine powder composition prepared using a monophasicreaction, a bi-phasic reaction, or a combination thereof. In certainother non-limiting embodiments of the present invention, thenutritional, nutraceutical, or pharmaceutical composition comprises aphosphatidylserine powder composition prepared using a mono-phasicreaction and purified using an organic solvent. In certain othernon-limiting embodiments of the present invention, the organic solventis an alcohol solvent. In certain other non-limiting embodiments of thepresent invention, the nutritional, nutraceutical, or pharmaceuticalcomposition further comprises another phospholipid.

The present invention also provides a process for preparing aphosphatidylserine powder preparation comprising sieving aphosphatidylserine powder, wherein the resulting phosphatidylserinepowder preparation is any one of the phosphatidylserine powdercompositions disclosed above. In certain other non-limiting embodimentsof the present invention, the process comprises preparing thephosphatidylserine powder composition from a natural source, syntheticsource, semisynthetic source, or a combination thereof. In certain othernon-limiting embodiments of the present invention, the process comprisespreparing the phosphatidylserine powder composition using a monophasicreaction, a bi-phasic reaction, or a combination thereof. In certainother non-limiting embodiments of the present invention, the processcomprises preparing the phosphatidylserine powder composition using amono-phasic reaction. In certain other non-limiting embodiments of thepresent invention, the process comprises preparing thephosphatidylserine powder composition using a bi-phasic reaction.

In certain other non-limiting embodiments of the present invention, theprocess for preparing a phosphatidylserine powder preparation furthercomprises a dry milling step wherein the phosphatidylserine is driedthen milled to obtain a dry milled powder. In certain other non-limitingembodiments of the present invention, the phosphatidylserine is milledtogether with silicon dioxide, preferably 2% silicon dioxide. In certainother non-limiting embodiments of the present invention, the dry milledpowder is a free flowing powder. In certain other non-limitingembodiments of the present invention, the process for preparing aphosphatidylserine powder preparation further comprises a purificationstep using an organic solvent. In certain other non-limiting embodimentsof the present invention, the organic solvent is an alcohol solvent. Incertain other non-limiting embodiments of the present invention, thealcohol solvent is a C1-C6 alcohol. In certain other non-limitingembodiments of the present invention, the alcohol solvent is a C2-C3alcohol.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides PS powder composition comprising a PS inwhich the majority of the particles have a predetermined particle size.

According to some embodiments the predetermined particle size is 500microns or less, preferably 400 microns or less, preferably 450 micronsor less, more preferably 350 microns or less or 300 microns or less,even more preferably 250 microns or less or 200 microns or less, andmost preferably 150 microns or less.

According to some embodiments at least 80% (w/w) of the particles in thePS powder preparation have the predetermined size, at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w) and at times at least 99% (w/w).

The present invention provides phosphatidylserine powder compositioncomprising a phosphatidylserine, wherein at least 80% (w/w), at times atleast 85% (w/w), at times at least 90% (w/w), at times at least 95%(w/w), at times at least 97% (w/w), and at times at least 99% (w/w) ofthe phosphatidylserine powder composition has a particle size of 500microns or less.

The present invention provides phosphatidylserine powder compositioncomprising a phosphatidylserine, wherein less than 20% (w/w), at timesless than 15% (w/w), at times less than 10% (w/w), at times less than 8%(w/w), at times less than 5% (w/w), at times less than 3% (w/w) and attimes less than 1% (w/w) of the phosphatidylserine powder preparationhas particle size of above 500 microns.

According to some embodiments at least 80% (w/w), at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w), and at times at least 99% (w/w) of thephosphatidylserine powder composition has a particle size of 450 micronsor less.

According to some embodiments at least 80% (w/w), at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w), and at times at least 99% (w/w) of thephosphatidylserine powder composition has a particle size of 400 micronsor less.

According to some embodiments at least 80% (w/w), at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w), and at times at least 99% (w/w) of thephosphatidylserine powder composition has a particle size of 350 micronsor less.

According to some embodiments at least 80% (w/w), at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w), and at times at least 99% (w/w) of thephosphatidylserine powder composition has a particle size of 300 micronsor less.

According to some embodiments at least 80% (w/w), at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w) and at times at least 99% (w/w) of thephosphatidylserine powder composition has a particle size of 250 micronsor less.

According to some embodiments at least 80% (w/w), at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w) and at times at least 99% (w/w) of thephosphatidylserine powder composition has a particle size of 200 micronsor less.

According to some embodiments at least 80% (w/w), at times at least 85%(w/w), at times at least 90% (w/w), at times at least 95% (w/w), attimes at least 97% (w/w) and at times at least 99% (w/w) of thephosphatidylserine powder composition has a particle size of 150 micronsor less.

Particle size was tested based on Particle Size Distribution Estimationby Analytical Sieving USP 786 method I. Using this test method, particlesize is represented by the minimum square aperture through which theparticle can pass. For the purposes of the present invention, thismethod may be used to determine particle size irrespective of whatpercentage by weight of the sample has a particle size larger than 75microns. Mechanical sieving was performed using 100 grams of a drypowder sample. The sample was then sieved using US Sieve number 60 or EUsieve number 250. This sieve selection is able to test for a particlesize of 250 microns or less. One of ordinary skill in the art is able toselect the proper sieve in order to test for a variety of particlesizes. The cumulative percentage by weight of sample passing through thesieve is the percentage by weight of the sample having a particle size(or less) of the sieve size opening for the selected sieve. Samples wereagitated using manual tapping as the agitation method and agitated forfive minutes. Agitation cycles were repeated until the weight of thetest sieved did not change by more than 5% of the previous weight onthat sieve. Particle size results were disregarded if particles wereobserved to be aggregated after agitation and testing was repeated.

As used herein the terms “phosphatidylserine” and “PS” usedinterchangeably, should be understood to encompass a lipid of thegeneral formula:

wherein the substituents, (substituent on position sn-1) and R₂(substituent on position sn-2), are independent of each other and areselected from H or an acyl group selected from saturated,mono-unsaturated and polyunsaturated fatty acids and X is serine, i.e.—CH₂CH(COOH)NH₂.

The sn-1 and sn-2 positions as used herein and as indicated in aboveformula, refer to the respective carbon atoms on the glycerol backbonewherein R₁ and R₂, are substituted on the corresponding acyl groups.

In the present invention, the terms “substituted” and its lingualequivalents and the term “conjugated” and its lingual equivalents areinterchangeably used and should be understood to encompass a fatty acidacyl covalently attached to the glycerophospholipid backbone of a serineglycerophospholipid of the invention. As noted above, the fatty acid maybe attached to the sn-1 and/or sn-2 positions.

As used herein, the term “fatty acid” should be understood to encompassa carboxylic acid with a long unbranched aliphatic tail (chain), whichis either saturated or unsaturated having one unsaturated bond(mono-unsaturated fatty acids) or two or more unsaturated bonds(poly-unsaturated fatty acids). When referring to a “fatty acid acyl” itshould be understood to encompass an —C(═O)—R radical wherein R is along unbranched aliphatic tail, which is either saturated or unsaturatedhaving one unsaturated bond (mono-unsaturated fatty acids) or two ormore unsaturated bonds (poly-unsaturated fatty acids).

Non-limiting examples of saturated fatty acids include: Butyric acid(Butanoic acid, C4:0), Caproic acid (Hexanoic acid, C6:0), Caprylic acid(Octanoic acid, C8:0), Capric acid (Decanoic acid, C10:0), Lauric acid(Dodecanoic acid, C12:0), Myristic acid (Tetradecanoic acid, C14:0),Palmitic acid (Hexadecanoic acid, C16:0), Stearic acid (Octadecanoicacid, C18:0), Arachidic acid (Eicosanoic acid, C20:0), Behenic acid(Docosanoic acid C22:0).

Non-limiting examples of unsaturated fatty acids include: Myristoleicacid (C14:1, ω-5), Palmitoleic acid (C16:1, ω-7), Oleic acid (C18:1,ω-9), Linoleic acid (C18:2, ω-6), Linolenic acid (C18:3)[Alpha-linolenic acid (C18:3, ω-3), Gamma-linolenic acid (C18:3, ω-6)],Eicosenoic acid (C20:1, ω-9), Arachidonic acid (C20:4, ω-6),Eicosapentaenoic acid (C20:5, ω-3), Erucic acid (C22:1, ω-9),Docosapentanoic acid (C22:5, ω-3) and Docosahexaenoic acid (C22:6, ω-3),Nervonic acid (C24:1, ω-9).

When referring to a “ . . . [fatty acid] conjugated to PS . . . ”, itshould be understood to encompass a PS wherein a fatty acid acyl isconjugated at position sn-1 and/or position sn-2 of the phospholipidbackbone (through the glycerol oxygen atom). In one embodiment a fattyacid is conjugated at position sn-1, and position sn-2 is eitherunsubstituted (e.g. having a hydrogen atom on the glycerol oxygen) orsubstituted with an acyl group selected from saturated, mono-unsaturatedand polyunsaturated fatty acids, which may be the same or different fromthe substitution on position sn-1.

In another embodiment a fatty acid is conjugated at position sn-2 andposition sn-1 is either unsubstituted (e.g. having a hydrogen atom onthe glycerol oxygen) or substituted with an acyl group selected fromsaturated, mono-unsaturated and polyunsaturated fatty acids, which maybe the same or different from the substitution on position sn-2.

The present invention also provides a nutritional, pharmaceutical, ornutraceutical composition or a functional or medical food comprising anyone of the phosphatidylserine powder compositions disclosed above.

The subject invention envisages that PS powder preparations withparticle size of 500 micron or less advantageously provide betterstability and homogenous properties when incorporated into nutritional,nutraceutical, or pharmaceutical compositions in comparison with PSpreparations with particle size of more than 500 micron.

Furthermore, the invention provides PS preparations with particle sizeof 500 micron or less which are produced through a monophasictransphosphatidylation process, and advantageously possess even betterstability and homogenous properties when incorporated into nutritional,nutraceutical, or pharmaceutical compositions, in comparison with PSpowder of the same particle size which is produced through a bi-phasictransphosphatidylation process.

The invention is advantageous compared to other existing commercial PSpowders. Upon mixing with powder nutritional, nutraceutical, orpharmaceutical compositions and dispersion in water, commercial PSpowders/PS preparations in which more than 20% (w/w) of the powder has aparticle size of above 500 microns tend to form non-homogenous mixtureswith floating particle and sediments and reduced PS stability. Similarnon-homogenous mixtures with reduced PS stability are also formed uponmixing commercial PS powders directly with water based nutritional,nutraceutical, or pharmaceutical compositions. Furthermore, the additionof conventional PS powders or PS preparations in which more than 20%(w/w) of the powder has a particle size of above 500 microns to chewablematrixes, such as candies or gummies, tend to reduce the elasticity andstability of said chewable nutritional, nutraceutical, or pharmaceuticalcompositions.

A nutritional composition as used herein can be any nutritionalcomposition including, but not limited to: human milk fat substitute,infant formula, adult formula, dairy product, including milk and dairydrinks, milk powder, drinks, shakes, ice cream, biscuit, soy product,bakery, pastry, bread, cake, sauce, soup, prepared food, includingprepared mashed vegetables and/or fruits, frozen food, condiment,confectionary, oil, fat, margarine, spread, filling, meat product,cereal, instant product, instant drink product, infant food, toddlerfood, bar, snack, candy, and chocolate product.

A nutraceutical composition as used herein can be any nutraceutical,which can be any substance that may be considered as a food or part of afood and provides medical or health benefits, including the preventionand treatment of diseases or disorders. Such nutraceutical compositionsinclude, but are not limited to: a food additive, a food supplement, adietary supplement, genetically engineered foods (such as for examplevegetables, herbal products, and processed foods such as cereals, soups,and beverages), stimulant functional food, clinical nutrition product,medical food, and pharmafood. Dietary supplements may be delivered inthe form of soft gel capsules, tablets, syrups, and other known dietarysupplement delivery systems.

The pharmaceutical or nutraceutical compositions may be in any of themany dosage delivery forms commonly used in the art. Pharmaceutical ornutraceutical compositions suitable for oral administration may bepresented as discrete dosage units (such as pills, tablets, pellets,dragees, capsules, or softgel), as a powder or granule, or as asolution, suspension, syrup, or elixir.

In a preferred embodiment, the nutraceutical composition is a powderdietary supplement or functional food intended to be mixed with water,water based dietary supplement, water based functional food, or achewable dietary supplement or functional food such as candy or gummy.

Preferably the nutritional or nutraceutical compositions further containat least one protein and at least one carbohydrate components.

A functional food as used herein can be any functional food, including,but not limited to, dairy product, ice-cream, biscuit, soy product,bakery, pastry, cakes and bread, instant product, sauce, soup, preparedfood, frozen food, condiment, confectionary, oils and fat, margarine,spread, filling, cereal, instant product, drinks and shake, infant food,bar, snack, candy and chocolate product.

Dietary supplements may be delivered in the form of pills, tablets,pellets, dragees, capsules, soft gels, sachet, syrups, and other knowndietary supplement delivery systems.

According to one embodiment the PS powder composition of the inventionis added to medical foods.

A medical food as used herein is specially formulated and intended forthe dietary management of a disease/disorder that has distinctivenutritional needs that cannot be met by normal diet alone.

According to one embodiment the present invention provide PS powder withbulk density with the range of 0.2-0.7 gr/ml, preferably 0.3-0.6 gr/ml,more preferably 0.35-0.55 gr/ml and most preferably 0.4-0.5 gr/ml.

In one embodiment, the PS powder preparation contains at least 10% w/wPS out of the preparation, preferably at least 20%, more preferably atleast 30% or 40%, even more preferably at least 50% or 60% and mostpreferably at least 70% or 80%.

According to another embodiment the PS concentration out of thenutraceutical composition is between 0.05% to10% W/W, preferably 0.1% to7%, more preferably 0.5% to 5% and most preferably 1% to 4%.

According to a further embodiment the PS dose in a nutraceutical dosageunit is between 10 mg to 1000 mg, preferably between 30 mg to 500 mg,more preferably between 40 mg to 300 mg and most preferably between 50mg to 100 mg of PS.

It should be noted that the PS preparation of the invention may alsocomprise other phospholipids, such as phosphatidylcholine (PC),phosphatidylethanolamine (PE), phosphatidyl-inositol (PI),phosphatidylglycerol (PG) and phosphatidic acid (PA), to which fattyacid acyls are covalently attached (bonded) at either or both of thesn-1 or sn-2 positions of the glycerol moiety of the phospholipid. Thefatty acid conjugation profile of any of the above-noted polar lipidsmay be the same as, or different from, the fatty acid conjugationprofile of PS, as disclosed herein.

The PS preparation of the invention is prepared from a natural,synthetic or semi-synthetic source or any combinations thereof. In anembodiment of the present invention, said natural source is derived fromany one of plant (such as for example soy or sunflower), non-mammaliananimal (such as for example krill, fish (such as for example Herring andblue Whiting)), or microorganism (such as for example bacteria) sourceor any combinations thereof.

Methods for preparing the PS powder preparation of the inventioninclude, but are not limited to:

-   -   1. Bi-phasic transphosphatidylation reaction in which the        reaction is carried out in a system containing aqueous and        organic mediums. Lecithin is being dissolved in the organic        phase while other ingredients such as phospholipase enzyme and        serine are dissolved in water (as described in U.S. Pat. No.        5,700,668).    -   2. Monophasic transphosphatidylation reaction in which the        reaction is carried out in an aqueous medium, the lecithin is        dispersed during the reaction and other ingredients such as        phospholipase enzyme and serine are dissolved in water (as        described in U.S. Pat. No. 6,492,146 and WO05068644).

Preferably, following the transphosphatidylation reaction additionalpurification steps using a solvent are added to the procedure.Preferably the solvent is an alcohol solvent, more preferably an alcoholsolvent with C1-C6 and most preferably an alcohol solvent with C2-C3.The solid is being dispersed with the solvent and stirred for one hour,preferably two hours and more preferably three hours and separation canbe achieved using a variety of filtration techniques including but notlimited to basket centrifuge, bowl centrifuge, decanter, etc., thesolids are being washed more than once, preferably twice, morepreferably three times and most preferably four times.

The obtained powder PS is dried using one of the following non-limitingtechnologies: vacuum oven, spray dryer, drum dryer, double cone dryer,paddle dryer, etc. and milled, optionally in one of the followingnon-limiting examples: Pin mill, Hammer mill, Cone mill, Jet mill, Bollmill, etc.

Preferably, following milling, the obtained PS powder is going through asieving stage using one of the following non limiting technologies: airclassifier, vibrating sieve, sifter, etc. to obtain PS powderpreparation with predetermined particle size.

In one embodiment, powder PS is being sieved using 500 microns screen,preferably 400 microns screen, more preferably 350 microns or 300microns, even more preferably 250 microns or 200 microns and mostpreferably 150 microns.

In another one of its aspects the invention provides a method ofimproving general health, cognitive functions and/or development, and/orimproving and/or preventing a condition in a subject suffering from acognitive disease or disorder comprising administering to a subject inneed thereof the PS preparation of the invention.

The invention further provides a use of a preparation of the inventionfor the manufacture of a nutraceutical or a medical food for improving acondition in a subject suffering from a cognitive disease or disorder.

The term “cognitive disease or disorder” as used herein should beunderstood to encompass any cognitive disease or disorder. Non-limitingexamples of such a cognitive disease or disorder are Attention DeficitDisorder (ADD), Attention Deficit Hyperactivity Disorder (ADHD),dyslexia, age-associated memory impairment, learning disorders, amnesia,mild cognitive impairment, cognitively impaired non-demented,pre-Alzheimer's disease, Alzheimer's disease, Parkinson's disease,pre-dementia syndrome, dementia, age related cognitive decline,cognitive deterioration, moderate mental impairment, mentaldeterioration as a result of aging, conditions that influence theintensity of brain waves and/or brain glucose utilization, stress,anxiety, depression, behavior disorders, concentration and attentionimpairment, mood deterioration, general cognitive and mental well-being,neurodegenerative disorders, hormonal disorders or any combinationsthereof. In a specific embodiment, the cognitive disorder is memoryimpairment.

The term “improving a condition in a subject suffering from a cognitivedisease or a cognitive disorder” as used herein should be understood toencompass: ameliorating undesired symptoms associated with a disease,disorder, or pathological condition; preventing manifestation ofsymptoms before they occur; slowing down progression of a disease ordisorder; slowing down deterioration of a disease or disorder; slowingdown irreversible damage caused in a progressive (or chronic) stage of adisease or disorder; delaying onset of a (progressive) disease ordisorder; reducing severity of a disease or disorder; curing a diseaseor disorder; preventing a disease or disorder from occurring altogether(for example in an individual generally prone to the disease) or acombination of any of the above. For example, in a subject sufferingfrom memory impairment, for example as a result of Alzheimer's Disease,symptoms including deterioration of spatial short-term memory, memoryrecall and/or memory recognition, focused and sustained attention,learning, executive functions and/or mental flexibility are improved byuse of a lipid preparation of the invention.

According to one embodiment the PS preparation of the invention is dryblended with a powder nutraceutical prior to mixing the nutraceuticalwith water.

According to another embodiment, the powder PS of the invention isblended with water based nutraceutical.

In yet another aspect of the invention, the PS preparation is beingadded to chewable matrix, such as candy or gummy.

The numerical values provided herein are representative of thoseemployed by the inventors for practicing and describing the preferredembodiments of the present invention. It should be appreciated thatwhile these values are exemplary of preferred embodiments for practicingand describing the invention, those skilled in the art, in light of thepresent disclosure, will recognize that these values are not intended tonecessarily require exact numerical precision and may be subject to areasonable degree of variability without departing from the spirit andintended scope of the invention.

The following Examples are representative of techniques employed by theinventors in carrying out aspects of the present invention. It should beappreciated that while these techniques are exemplary of preferredembodiments for the practice of the invention, those of skill in theart, in light of the present disclosure, will recognize that numerousmodifications can be made without departing from the spirit and intendedscope of the invention.

EXAMPLE 1

Production of PS powder using a monophasic reaction (sample No. 1). 140gr of an emulsion containing ethanol purified soy lecithin in water wasmixed with a solution containing 41 gr L-serine, 35 ml acetate bufferand 0.55 gr phospholipase-D enzyme and stirred at 40° C. After 36 hoursof stirring, the solution was filtered through a Buchner filter in orderto remove all water soluble components. The solids were dispersed in 140ml purified water for 30 minutes and filtered once again. The wet solidswere dried in a vacuum dryer to obtain dry PS powder with PSconcentration of 58.8% measured using HPLC. Dry powder was milledtogether with 2% silicon dioxide to obtain free flowing powder in whichmore than 20% (w/w) of the powder had particle size above 500 microns.

EXAMPLE 2

Sieving sample No. 1 (production of sample No. 2). Sample No. 1 wassieved through 250 microns screen to obtain powder in which 97% (w/w) ofthe powder had particle size of 250 microns or less.

EXAMPLE 3

Purification of sample No. 1 using alcohol solvents (production ofsample No. 3). 10 gr from sample No. 1 (before drying) were dispersed in40 ml ethanol and the solution was stirred for 30 minutes. The solutionwas filtered through a Buchner filter to separate between the solids andfiltrate. The solids were collected from the filter and the same processwas repeated two more times. Wet solids were dried in a vacuum dryer toobtain dry PS powder. Dry powder was milled together with 2% silicondioxide to obtain free flowing powder in which more than 20% (w/w) ofthe powder had particle size above 500 microns.

EXAMPLE 4

Sieving sample No. 3 (production of sample No. 4). Sample No. 3 wassieved through 250 microns screen in order to obtain powder in which 97%(w/w) of the powder had particle size of 250 microns or less.

EXAMPLE 5

Production of PS powder using a bi-phasic reaction (sample No. 5). 40 grof ethanol purified soy lecithin were dissolved in 400 ml hexane and26.4 gr MCT oil, the solution was concentrated up to total dryness. 132ml hexane and 50 ml ethyl acetate were added to create organic phase.112 ml purified water, 52 gr L-serine, 36 ml acetate buffer and 2 grphospholipase-D enzyme were mixed together to create the aqueous phase.The two phases were stirred for 36 hours at 40° C. After stoppingstirring, two phases were formed. The lower phase was removed and theupper phase was concentrated up to total dryness. The oil was mixed with500 ml of ethanol for 30 minutes and filtered through a Buchner filterin order to create powder. The cake was collected and re-washed withadditional 500 ml. The re-wash was repeated once more in the samemanner. Wet solids were dried in a vacuum dryer to obtain dry PS powder.Dry powder was milled together with 2% silicon dioxide to obtain freeflowing powder in which more than 20% (w/w) of the powder had particlesize above 500 microns.

EXAMPLE 6

Sieving sample No. 5 (production of sample No. 6). Sample No. 5 wassieved through 250 microns screen to obtain powder in which 97% (w/w) ofthe powder had particle size of 250 microns or less.

EXAMPLE 7

Floating and sedimentation properties of dry blends of different PSpowders with a nutritional composition (Similac®) following dispersion.100 mg PS powder from each sample (1-6) were blended with 9.9 grcommercial infant formula (Similac®) by a gentle mixing process. Theblended material was dispersed in 60 ml purified water. Table No. 1describes the floating and sedimentation properties of the dispersedblends. Advantageously, samples No. 2, 4 and 6 resulted in a solutionwith improved homogenous appearance. The homogenous appearance of thesolution containing sample No. 4 was improved even in comparison withsolutions containing samples No. 2 or 6.

TABLE 1 Appearance of nutraceutical containing PS powder of samples 1-6Sample Floating Homogenous No. particles Sedimentation appearance 1 + +− 2 − + + 3 + + − 4 − − ++ 5 + + − 6 + − +

EXAMPLE 8

Production of gummies containing powder PS. Gummies were produced usingconventional methods as described in Handbook of food science,technology and engineering, volume 3, Chapter 140 page 26. PS powderdispersed in water was added prior to the gelation of the pectin (justbefore the addition of citric acid).

EXAMPLE 9

Texture analysis of dummies containing PS powder of the invention incomparison with conventional PS powder. Gummies, produced as describedin example 8 in a lab scale, and containing either 4.5% PS powderaccording to the invention (sample No. 4) or other PS (sample No. 3),were analyzed for their appearance and stability. As demonstrated inTable 2, gummies containing PS powder of the invention had betterappearance and stability in comparison with gummies containing other PSpowder composition.

TABLE 2 Appearance and stability of gummies containing PS powder ofsamples No. 3 or 4 Appearance Hardness Gummies containing the PS UniformStable and elastic powder of sample No. 4 during storage Gummiescontaining the PS Non uniform Cracks were observed powder of sample No.3 during storage

The claims are:
 1. A phosphatidylserine powder composition comprising aphosphatidylserine, wherein at least 80% (w/w) of the phosphatidylserinepowder composition has a particle size of 500 microns or less.
 2. Aphosphatidylserine powder composition comprising a phosphatidylserine,wherein less than 20% (w/w) of the phosphatidylserine powder compositionhas a particle size of above 500 microns.
 3. The phosphatidylserinepowder composition of claim 1, wherein at least 97% (w/w) of thephosphatidylserine powder composition has a particle size of 250 micronsor less.
 4. The phosphatidylserine powder composition of claim 1,wherein the phosphatidylserine is prepared using a monophasic reaction.5. The phosphatidylserine powder composition of claim 4, wherein thephosphatidylserine is purified using an organic solvent.
 6. Thephosphatidylserine powder composition of claim 5, wherein the organicsolvent is an alcohol solvent.
 7. The phosphatidylserine powdercomposition of claim 1, wherein the phosphatidylserine is prepared usinga bi-phasic reaction.
 8. The phosphatidylserine powder composition ofclaim 1, wherein the powder composition when mixed in water withoutprocessing by high pressure homogenization, disperses more homogeneouslyand demonstrates reduced sedimentation compared to a PS preparation inwhich more than 20% (w/w) of the PS preparation has a particle size ofabove 500 microns.
 9. The phosphatidylserine powder composition of claim1, wherein the powder composition is mixed with a powder nutritional,nutraceutical, or pharmaceutical composition to form a mixture that whenmixed with water without processing by high pressure homogenization, themixture disperses more homogeneously and reduces sedimentation comparedto a mixture of the powder nutritional, nutraceutical, or pharmaceuticalcomposition and a PS preparation in which more than 20% (w/w) of the PSpreparation has a particle size of above 500 microns.
 10. Thephosphatidylserine powder composition of claim 1, wherein the powdercomposition when mixed without processing by high pressurehomogenization with a liquid nutritional, nutraceutical, orpharmaceutical composition disperses more homogeneously and demonstratesreduced sedimentation compared to a PS preparation in which more than20% (w/w) of the PS preparation has a particle size of above 500microns.
 11. A nutritional, nutraceutical, or pharmaceutical compositioncomprising the phosphatidylserine powder composition of claim
 1. 12. Thecomposition of claim 11, wherein the nutraceutical or pharmaceuticalcomposition is a pill, tablet, pellets, dragees, capsule, softgel, orsyrup.
 13. The composition of claim 11, wherein the nutritional ornutraceutical composition is a baby formula, adult formula, or a medicalnutrition product.
 14. The composition of claim 11, wherein thenutritional, nutraceutical, or pharmaceutical composition is a candy,gummy, or confectionary.
 15. The composition of claim 14, wherein thegummy maintains a uniform appearance and elastic stability duringstorage.
 16. The composition as in claim 11, wherein the bulk density ofthe phosphatidylserine powder composition is 0.2 to 0.7 g/ml.
 17. Thecomposition as in claim 11, wherein the dosage unit of thephosphatidylserine powder composition is 10 mg to 1000 mg.
 18. Thecomposition of claim 11, wherein the nutritional, nutraceutical, orpharmaceutical composition is a liquid.
 19. The composition of claim 11,wherein the nutritional, nutraceutical, or pharmaceutical composition isa powder.
 20. The composition as in claim 11, wherein the nutritional,nutraceutical, or pharmaceutical composition contains at least oneprotein and at least one carbohydrate.
 21. The composition of claim 11,wherein the phosphatidylserine powder is at least 0.05% (w/w) of thenutritional, nutraceutical, or pharmaceutical composition.
 22. Thecomposition of claim 11, wherein the phosphatidylserine is preparedusing a monophasic reaction.
 23. The composition of claim 22, whereinthe phosphatidylserine is purified using an organic solvent.
 24. Thecomposition of claim 23, wherein the organic solvent is an alcoholsolvent.
 25. The composition of claim 11, wherein the phosphatidylserineis prepared using a bi-phasic reaction.
 26. A process for preparing aphosphatidylserine powder preparation comprising sieving aphosphatidylserine powder, wherein the resulting phosphatidylserinepowder preparation is the phosphatidylserine powder composition ofclaim
 1. 27. The process for preparing a phosphatidylserine powderpreparation of claim 26, wherein the phosphatidylserine is producedusing a monophasic reaction.
 28. The process for preparing aphosphatidylserine powder preparation of claim 27, wherein thephosphatidylserine is purified using an organic solvent.
 29. The processfor preparing a phosphatidylserine powder preparation of claim 26,wherein the phosphatidylserine is produced using a bi-phasic reaction.30. The process for preparing a phosphatidylserine powder preparation ofclaim 26, further comprising a dry milling step wherein thephosphatidylserine is dried then milled to obtain a dry milled powder.31. The process for preparing a phosphatidylserine powder preparation ofclaim 30, wherein the phosphatidylserine is milled together with silicondioxide.
 32. The process for preparing a phosphatidylserine powderpreparation of claim 30, wherein the dry milled powder is a free flowingpowder.
 33. The process for preparing a phosphatidylserine powderpreparation of claim 26, further comprising a purification step using analcohol solvent.
 34. The process for preparing a phosphatidylserinepowder preparation of claim 33, wherein the alcohol solvent is a C1-C6alcohol.
 35. The process for preparing a phosphatidylserine powderpreparation of claim 33, wherein the alcohol solvent is a C2-C3 alcohol.